Kidney diseases affect >10% of adults worldwide but fundamental understanding of kidney pathogenesis relies on high-cost and less-accessible radiological imaging techniques. A possible alternative, in vivo noninvasive fluorescence imaging, falls short as a low-cost, high-sensitivity tool for longitudinal evaluation of kidney function of small animals. Noninvasive fluorescence kidney functional imaging is deficient, not due to the limited penetration depth of the light, but rather the undesired rapid accumulation of conventional organic fluorophores in background tissues.
Development of low-cost imaging techniques for noninvasive longitudinal assessment of individual kidney function is indispensable to understand the pathogenesis of kidney disease and accelerate drug discovery. In both clinical practice and preclinical research, measuring blood urea nitrogen (BUN) and serum creatinine (Scr) concentrations is the most common and low-cost method for evaluation of kidney function. However, blood tests often fail to identify the kidney function changes at an early asymptomatic stage, particularly in unilateral renal disease where a contralateral kidney functions well. To address this challenge, renography, a noninvasive kidney functional imaging technique, has been widely used in longitudinal monitoring of disease progresses of individual kidneys at high spatial and temporal resolution,4 which generally includes the following steps: 1) continuous imaging of kidneys for ˜60 min right after intravenous (i.v.) injection of a renal clearable probe; 2) conversion of the obtained images to time-intensity curves of each kidney (renograms); 3) derivation of accumulation and clearance kinetics of the injected probe from renograms. Since accuracy of kidney functional evaluation requires imaging of accumulation and clearance of renal clearable probes in the kidneys at high contrast and high temporal resolution, very few probes except radiotracers can meet this requirement even in the preclinical research. However, high cost and potential radiation exposure make radiological imaging techniques less accessible for most researchers and severely limit fundamental understanding of kidney diseases.
In vivo NIR fluorescence imaging allows visualization of biological processes in intact living animals at high spatial and temporal resolution. This technique has been widely used in preclinical disease studies due to its low cost, high sensitivity and the absence of radiation. However, translation of fluorescence techniques into noninvasive kidney functional imaging remains highly challenging. Due to extremely low contrast in noninvasive images of the kidney, kidney fluorescence imaging studies which utilize renal clearable organic fluorophores as contrast agents suffer one of two possible restrictions: (1) the studies must be conducted invasively (the kidneys are surgically exposed); or (2) the fluorophores must be conjugated with ligands which target specific receptors in the kidneys.